Canonical features of human antibodies recognizing the influenza hemagglutinin trimer interface.
J Clin Invest
; 131(15)2021 08 02.
Article
en En
| MEDLINE
| ID: mdl-34156974
ABSTRACT
Broadly reactive antibodies targeting the influenza A virus hemagglutinin (HA) head domain are thought to be rare and to require extensive somatic mutations or unusual structural features to achieve breadth against divergent HA subtypes. Here we describe common genetic and structural features of protective human antibodies from several individuals recognizing the trimer interface (TI) of the influenza A HA head, a recently identified site of vulnerability. We examined the sequence of TI-reactive antibodies, determined crystal structures for TI antibody-antigen complexes, and analyzed the contact residues of the antibodies on HA to discover common genetic and structural features of TI antibodies. Our data reveal that many TI antibodies are encoded by a light chain variable gene segment incorporating a shared somatic mutation. In addition, these antibodies have a shared acidic residue in the heavy chain despite originating from diverse heavy chain variable gene segments. These studies show that the TI region of influenza A HA is a major antigenic site with conserved structural features that are recognized by a common human B cell public clonotype. The canonical nature of this antibody-antigen interaction suggests that the TI epitope might serve as an important target for structure-based vaccine design.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Glicoproteínas Hemaglutininas del Virus de la Influenza
/
Subtipo H1N1 del Virus de la Influenza A
/
Anticuerpos Neutralizantes
/
Anticuerpos Antivirales
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Clin Invest
Año:
2021
Tipo del documento:
Article